Increased expression of angiopoietin-2 and Tie2 receptor in a rat model of myocardial ischaemia/reperfusion

Abstract

The angiopoietins and Tie receptors are involved in blood vessel formation. The role of the angiopoietin/Tie receptor system in myocardial ischaemia/reperfusion is not well known. To investigate the participation of angiopoietins and Tie receptors in myocardial ischaemia/reperfusion, adult Wistar rats were studied in which the left coronary artery was ligated for 30 min, followed by reperfusion. Angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), Tie1 and Tie2 were measured immediately after relief of occlusion, and 1, 6, 24 and 72 h after reperfusion, by Northern blot, Western blot and immunohistochemical staining. Ang2 mRNA was increased significantly at 24 h and 48 h after reperfusion, and returned to baseline levels at 72 h, in the jeopardized myocardium. Tie2 mRNA increased 3.4-fold immediately after the relief of occlusion, reached a maximum 8-fold increase at 24 h after reperfusion and remained elevated up to 72 h. Ang2 protein levels also increased after reperfusion, reaching a maximum 2.2-fold increase at 48 h after reperfusion. Tie2 protein increased immediately after relief of ischaemia, and showed a significant increase from 6 h to 72 h after reperfusion as compared with the sham control. Ang1 and Tie1 mRNA and protein did not show significant changes after ischaemia/reperfusion. Immunohistochemical studies also showed increased immunoreactivity of Ang2 and Tie2 in the jeopardized myocardium after ischaemia/reperfusion. In conclusion, expression of both Ang2 and Tie2 increased after ischaemia/reperfusion in the rat ventricular myocardium, while the expression of Ang1 and Tie1 did not.